There is evidence that nervous system mast cells may play a role in the pathogenesis of the experimental autoimmune demyelinating diseases, experimental allergic neuritis (EAN), and experimental allergic encephalomyelitis (EAE). We compared mast cell numbers in the peripheral nervous system (PNS) and central nervous system (CNS) of rodent strains that differed in their susceptibility to experimental demyelination. Mast cells were counted by toluidine blue staining of formalin-fixed tissue. Normal Lewis rats (susceptible to both EAN and EAE) had significantly greater numbers of mast cells in the dura mater (about 6x) of the meninges and the sciatic nerve (3x) than Brown Norway rats (resistant to EAE and EAN induction under normal circumstances). Similarly SJL/J mice (susceptible to EAE and EAN) had significantly greater numbers of CNS (3x) and PNS (8x) mast cells than C3H mice (more resistant to disease induction). Other mouse strains were also examined, and PNS mutant Trembler mice had high numbers of PNS mast cells, while the mast cell deficient W/Wv mice contained no detectable mast cells in either the CNS or PNS. Reconstitution of W/Wv mast cells was accomplished by intravenous injection of bone marrow cells from congenic littermates. After seven months, mast cells could be seen in both the CNS and PNS of reconstituted animals. The possibility that mast cells and mast cell precursors can migrate into the nervous system of animals, in the absence of inflammatory disease, may have implications for their role in the pathogenesis of experimental demyelinating diseases.